ABSTRACT: The purpose of this proposal is to obtain funds for the purchase of an Illumina NextSeq 550 system ? an integrated platform that uses massively parallel nucleic acid sequencing technology for genetic analysis and functional genomics. The NextSeq 550 was released in 2016 as the newest instrument in the Illumina product line. The key features of the instrument include (i) relatively long reads at high output (2 x 150 bases/read, and up to 400 million reads in a single run); (ii) the broadest application flexibility (genome sequencing, epigenomics, transcriptional analysis, RNA sequencing, protein?nucleic acid interactions; (iii) ease of operation and high flexibility to meet the demands of different users. The key advantages of NextSeq 550 over other next generation sequencing (NGS) instruments in this price range is the lower cost of operation, high quality of reads and fast turnaround time. The only NGS instrument that is currently at Stony Brook University (SBU) is the older version of MiSeq, which is not capable of running most of the highly-demanded NGS applications such as mRNA sequencing or whole human genome sequencing. This proposal originates from nine major and two minor users from six departments of SBU and Stony Brook Cancer Center. The NIH funding of major and minor users spans to 2019 - 2022. The range of projects detailed in this proposal is wide and the necessity of having the NGS technology locally is clear. The projects described herein are likely to benefit dramatically from the availability of a NextSeq 550 at the SBU Genomics Core Facility. The instrument will be used for pilot projects that contain human or non-human specimen, for projects where turnaround time is crucial and for education. For large-scale high- throughput sequencing projects SBU will continue using outside NGS resources (New York Genome Center). The Genomics Core Facility already has the infrastructure in place to operate and maintain the instrument. SBU is extremely supportive, providing matching funds of $190K in order to establish a NGS system at the Genomics Core. Operation of the system will be provided by Illumina-trained technical specialists, and the Genomics Core in collaboration with the Data Science and Biostatistics Core will provide assistance to users in experiment planning, data quality control and bioinformatics data analysis. The NextSeq 550 will also be used for educational purposes, uniting students and faculty members from all Departments of SBU interested in genomics. The NextSeq 550 will allow the participating users to run a broad variety of NGS applications at a lower cost and with the shortest turnaround time. Furthermore, this will be the only instrument on SBU campus that has the capacity for whole genome - wide experiments, and it will allow many scientists to do their first next generation sequencing experiments, resulting in greater likelihood of success for further NIH funding.